Targeted fever management versus no temperature management and sedation versus early awakening after cardiac arrest. A 2x2 factorial randomized clinical trial

Background: Cardiac arrest (CA) patients have high risk of death and cognitive impairment.

Targeted temperature management (TTM) has been introduced in clinical practice to improve outcome, but the certainty of evidence is low. Sedation has been introduced as part of TTM, but also for presumed brain protective effects.

From two trials (TTM1 and 2) we conclude that cooling to hypothermic temperatures does not confer benefit compared to treating fever and keeping normothermia.

Our aim is to answer whether TTM to avoid fever and protocolized mandatory sedation are beneficial interventions compared to no TTM and early awakening.PICO: In unconscious adult patients after out of hospital cardiac arrest, is TTM compared to no TTM and protocolized mandatory sedation compared to early awakening beneficial in terms of survival, functional status and quality of life (QoL).Design: International, assessor-blinded, factorial, randomized trial recruiting 3100 CA participants.

Primary outcome is landmark mortality at 6 months.

Surviving patients and relatives will be asked to visit blinded assessments to assess cognitive status and QoL at 6 months.Relevance: TTM and sedation regimens are potential interventions in an area where beneficial therapies are lacking, but the overall evidence is insufficient.

With experience from large international cardiac arrest trials, our network will have unique possibilities to inform practice with relevance for patients, relatives, health economy and society.